Empagliflozin in Patients with Chronic Kidney Disease

Abstract

Background: The effects of empagliflozin in patients with chronic kidney disease who are at risk for disease progression are not well understood. The EMPA-KIDNEY trial was designed to assess the effects of treatment with empagliflozin in a broad range of such patients.

Methods: We enrolled patients with chronic kidney disease who had an estimated glomerular filtration rate (eGFR) of at least 20 but less than 45 ml per minute per 1.73 m² of body-surface area, or who had an eGFR of at least 45 but less than 90 ml per minute per 1.73 m² with a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of at least 200. Patients were randomly assigned to receive empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in eGFR to <10 ml per minute per 1.73 m², a sustained decrease in eGFR of ≥40% from baseline, or death from renal causes) or death from cardiovascular causes.

Results: A total of 6609 patients underwent randomization. During a median of 2.0 years of follow-up, progression of kidney disease or death from cardiovascular causes occurred in 432 of 3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results were consistent among patients with or without diabetes and across subgroups defined according to eGFR ranges. The rate of hospitalization from any cause was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P = 0.003), but there were no significant between-group differences with respect to the composite outcome of hospitalization for heart failure or death from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the placebo group) or death from any cause (in 4.5% and 5.1%, respectively). The rates of serious adverse events were similar in the two groups.

Conclusions: Among a wide range of patients with chronic kidney disease who were at risk for disease progression, empagliflozin therapy led to a lower risk of progression of kidney disease or death from cardiovascular causes than placebo. (Funded by Boehringer Ingelheim and others; EMPA-KIDNEY ClinicalTrials.gov number, NCT03594110; EudraCT number, 2017-002971-24.).

Figure 1

The primary outcome of kidney disease progression or death from cardiovascular causes occurred in 432 participants (13.1%) in the empagliflozin group and 558 participants (16.9%) in the placebo group. This represented 42 fewer primary outcomes per 1000 patients treated for 2 years.

Figure 2

The primary outcome of kidney disease progression or death from cardiovascular causes occurred in 432 participants (13.1%) in the empagliflozin group and 558 participants (16.9%) in the placebo group. This represented 42 fewer primary outcomes per 1000 patients treated for 2 years.

Figure 3. Effect of allocation to empagliflozin on estimated glomerular filtration rate

Shown are forest plots of the hazard ratios for the primary outcome according to key prespecified baseline subgroups (with the diamond representing the overall result). Hazard ratios, confidence intervals, and P values were estimated with the use of Cox proportional-hazards regression models, adjusted for age, sex, prior diabetes, estimated glomerular filtration rate (GFR), urinary albumin-to-creatinine ratio (ACR) and region. Tests for heterogeneity or trend in the hazard ratio for subgroups were estimated through the inclusion of relevant interaction terms. Error bars presented are 95% confidence intervals.